Biology subjects

Dubois, B.

Publications and source records attributed to Dubois, B..

11 recordsLinked to original sources

bioRxiv2026

Episodic memory ERPs reflect preclinical Alzheimers disease progression

Structured AbstractO_ST_ABSBackgroundC_ST_ABSAlzheimers disease (AD) neuropathology emerges decades before symptoms, requiring sensitive, non-invasive markers for early diagnosis. We investigated behavioural and EEG markers of episodic memory in cognitively normal older adults at-risk for AD. MethodsForty-five INSIGHT-preAD cohort participants (15 progressors to prodromal AD, 15 stable {beta}-amyloid positive [A{beta}+] participants, 15 controls [A{beta}-]) completed an Old/New word recognition task during high-density EEG. Behavioural performance and memory-related evoked-related potentials (ERPs; P3, FN400, P600, post-retrieval monitoring) were analysed longitudinally over 5 years. ResultsProgressors showed significantly reduced accuracy, sensitivity, and slower responses. They showed attenuated FN400, P600, and monitoring amplitudes over left parieto-occipital regions. Source analysis revealed hypoactivation in the left inferior frontal and right posterior cingulate cortex, across components with additional disruption during P600. Stable A{beta}+ individuals showed milder P600 hypoactivations. DiscussionBehavioural and ERP alterations preceded clinical decline, supporting EEG-based markers of episodic memory decline for preclinical AD risk stratification.

neuroscience↗

bioRxiv2026

Benchmarking full-length ITS metabarcoding across Illumina 2x500, PacBio, and Oxford Nanopore sequencing using mock and soil communities

Metabarcoding is a powerful tool for biodiversity comparisons, where standard-size DNA barcodes (>500 bases) offer better taxonomic resolution than shorter ones. Still, the choice of sequencing platforms and bioinformatics pipelines may strongly affect inferred diversity due to various technical biases. We assessed the relative performance of Illumina MiSeq i100 (2x500 paired-end), PacBio Revio and Oxford Nanopore MinION sequencing and bioinformatics pipelines, using full-length ITS amplicon sequencing datasets from a 103-species mock community and 45 composite soil samples. Despite numerous low-quality reads, PacBio yielded the lowest overall error rate and highest number of taxa. Illumina revealed the highest proportion of chimeric and index-switched reads, along with a strong bias towards shorter amplicons. MinION data analysed using PRONAME and Minovar - a bioinformatics pipeline presented here - had the largest proportion of low-quality data, and rare taxa were lost during data filtering and read polishing steps. Although Minovar enabled amplicon sequence variant (ASV) level precision for common taxa, we recommend clustering ASVs into OTUs. For PacBio, standard filtering approaches outperformed the ASV approach because they retained rare taxa. For Illumina, a stringent ASV approach or removal of rare OTUs would limit artefacts. Across all platforms, excess PCR cycles promoted chimeric and low-quality reads and lost quantitativity in biodiversity assessments. With moderate differences in effect sizes, all analytical approaches supported the conclusion that sampling design determines how we see soil biodiversity responses to land use. For biodiversity surveys based on the full-length ITS metabarcoding, we recommend using PacBio sequencing with standard, non-ASV pipelines.

bioinformatics↗

bioRxiv2025

Benchmarking long-read RNA-sequencing technologies with LongBench: a cross-platform reference dataset profiling cancer cell lines with bulk and single-cell approaches

Long-read RNA sequencing enables full-length transcript profiling and improved isoform resolution, but variable platforms and evolving chemistries demand careful benchmarking for reliable application. We present LongBench, a matched, multi-platform reference dataset spanning bulk, single-cell, and single-nucleus transcriptomics across eight human lung cancer cell lines with synthetic spike-in controls. LongBench in-corporates three state-of-the-art long-read protocols alongside Illumina short reads: Oxford Nanopore Technologies (ONT) PCR-cDNA, ONT direct RNA, and PacBio Kinnex. We systematically evaluate transcript capture, quantification accuracy, differential expression, isoform usage, variant detection, and allele-specific analyses. Our results show high concordance in gene-level differential analyses across protocols, but reduced consistency for transcript-level and isoform analyses due to length- and platform-dependent biases. Single-cell long-read data are highly concordant with bulk for high-confidence features, though single-nuclei data show reduced feature detection. LongBench provides one of the largest publicly available long-read benchmarking resources, enabling rigorous cross-platform evaluation and guiding technology selection for transcriptomic research.

genomics↗

bioRxiv2025

Spatial tumour-immune ecosystems shape the efficacy of anti-PD1 immunotherapy in primary cutaneous melanoma

Intra-tumoral heterogeneity in melanoma arises from dynamic cancer cell plasticity and underlies various mechanisms of immune escape. Here, we combined high-plex immunofluorescence imaging with spatially resolved transcriptomics to map the architecture of melanoma cell states and their interactions with the immune microenvironment in primary cutaneous tumours prior to adjuvant anti-PD1 immune checkpoint inhibitor (ICI) treatment. Computational analyses showed that melanoma cells organise into spatially restricted patches, with a preferential organisation of undifferentiated cells associated with poor ICI efficacy. Neighbouring immune cell composition varied according to cancer cell states, with a crucial involvement of specific subsets of tumour-associated macrophages, driven by signalling pathways involving tumour-derived and microenvironmental cues such as IFN-{gamma} and hypoxia. Integrated spatial analyses further revealed tumour-immune ecosystems that stratify patient outcomes, delineating configurations either associated with ICI efficacy or metastatic relapse. These results uncover the spatial landscape of tumour ecosystems and identify signalling pathways as potential targets for improving the efficacy of ICI in melanoma. HighlightsO_LIMelanoma cell states spatial organization is associated with aPD1 therapy efficacy C_LIO_LISpatial organization of TAM subsets is a crucial determinant of ICI outcome C_LIO_LIMelanoma cells in different states co-localise with functionally distinct TAM subsets C_LIO_LIIdentification of cell-cell communication pathways that underlie tumour-TAM crosstalk C_LIO_LIA balance between tumour-immune ecosystems is associated with aPD1 therapy efficacy C_LI

cancer biology↗

bioRxiv2024

Deciphering the tumor-infiltrating CD73+ regulatory gammadelta T cell ecosystem associated with poor survival of patients with ovarian cancer

The ability of tumor cells to overcome immune surveillance is an essential step in tumor development and progression. Among the immune cells playing a role in tumor control, {gamma}{delta} T cells contribute to the immune response against many tumor types through their direct cytotoxic activity against cancer cells and their capacity to regulate the functions of other immune cells. However, their presence in the tumor microenvironment is also associated with poor prognosis, suggesting that {gamma}{delta} T cells may also have pro-tumor activities. We previously described a regulatory {gamma}{delta} T-cell subset that expresses CD73 and produces IL-10, IL-8 and adenosine. Here, we report a higher CD73+ {gamma}{delta} T cell density in the tumor microenvironment of ovarian cancer samples from patients with short-term than long-term survival. Starting from this original observation, we investigated their neighborhood and described a specific ecosystem according to their pro-tumor functions.

cancer biology↗

bioRxiv2024

Spatial architecture of CD8+ T cells and DC subsets is critical for the response to immune checkpoint inhibitors in melanoma

BackgroundDendritic cells (DCs) are promising targets for cancer immunotherapies owing to their central role in the initiation and the control of immune responses. Their functions encompass a wide range of mechanisms mediated by different DC subsets. Several studies have identified human tumor- associated DC (TA-DC) populations through limited marker-based technologies, such as immunostaining or flow cytometry. However, tumor infiltration, spatial organization and specific functions in response to immunotherapy of each DC subset remain to be defined. MethodsHere, we implemented a multiplexed immunofluorescence analysis pipeline coupled with bio-informatic analyses to decipher the tumor DC landscape and its spatial organization within melanoma patients lesions, and its association with patients response to immune checkpoint inhibitors (ICI). For this aim, we analyze a cohort of 41 advanced melanoma patients treated with anti- PD1 alone or associated with anti-CTLA4. Distance and cell network analyses were performed to gain further insight into the spatial organization of tumor-associated DCs. A Digital Spatial Profiling analysis further characterized ecosystem of tumor-infiltrating DCs. ResultsPlasmacytoid DCs (pDCs) were the most abundant DC population, followed by conventional cDC1 and mature DCs, present in equal proportions. In contrast to CD8+ T cell frequency, and despite varying densities, all DC subsets were associated with a favorable response to ICI. Distance and cell network analyses demonstrated that tumor-infiltrating DCs were largely organized in dense areas with high homotypic connections, except for cDC1 that exhibited a more scattered distribution. We identified four patterns of ecosystems with distinct preferential interactions between DC subsets. Significantly, the proximity and interactions between CD8+ T cells and cDC1 were positively associated with patients response to ICI. ConclusionsOur study unravels the complex spatial organization of DC subsets and their interactions in melanoma patient lesions, shedding light on their pivotal role in shaping the response to ICI. Our discoveries regarding the spatial arrangement of cDC1, especially with CD8+ T cells, provide valuable clues for improving immunotherapeutic strategies in melanoma patients. What is already known on this topicDendritic cells (DCs) are promising targets for cancer immunotherapies owing to their central role in the initiation and the control of immune responses. Although conventional type 1 dendritic cells (cDC1) were proposed to contribute to immunotherapy response, their precise functions and interactions with other immune populations in human cancers are largely unknown. What this study addsThis study provides a precise characterization of the spatial distribution and organization of tumor- infiltrating DCs in a large cohort of advanced melanoma patients, and in correlation with response to immunotherapy. While DCs are organized in dense areas with high homotypic connections, cDC1 exhibit a more scattered distribution and form heterotypic aggregates with other DC subsets. More importantly, a close connection between cDC1 and CD8 T cell is uniquely correlated with the patients response to immunotherapy. How this study might affect research, practice or policyThis study improves our understanding of CD8-DC spatial organization within the tumor microenvironment and will have a broad spectrum of implications in the design of anti-tumor immune-activating compounds and the design of biomarkers of response to immunotherapy for melanoma patients.

cancer biology↗

bioRxiv2022

EEG-neurofeedback for promoting neuromodulation in the elderly: evidence from a double-blind study

BackgroundElectroencephalography (EEG) is a non-invasive method that records the brain signals with time resolution in the millisecond range, thereby allowing the monitoring of subjects mental states in real time. Using appropriate biomarkers extracted from these EEG signals and presenting them back in a neurofeedback loop can foster neural compensation mechanisms by teaching subjects to modulate their brain activity. Over the last decades, several neural biomarkers of aging have been described, with growing evidence suggesting that neuromodulation may have an important role in regulating brain activity in the elderly. Methods and objectivesWe used three neural biomarkers of aging, namely the Peak Alpha Frequency, the Gamma-band synchronization, and the Theta/Beta ratio, in the framework of an EEG-based brain-computer interface, with two main objectives: 1) to test whether healthy elderly people with subjective memory complaints may learn to modulate their brain activity through EEG-neurofeedback training in a double-blind, placebo-controlled study; and 2) whether that neuromodulation may have a positive impact on subjects cognition. ResultsA significant self-modulation of two neural biomarkers that usually decline with age was observed exclusively in the group of subjects who underwent the EEG-neurofeedback training, in clear contrast with the subjects who received the sham feedback. This neuromodulation did not have a direct effect on subjects cognitive abilities, as measured by neuropsychological tests pre-versus post-training, probably because all the subjects accurately performed these tests already at study entry (i.e., pre-training). ConclusionThe results of this double-blind study are in line with one of the main criteria for successful neuromodulation, thus encouraging research on EEG-neurofeedback as a promising non-pharmacological intervention for promoting self-regulation of brain activity with a view to improve cognitive aging.

neuroscience↗

bioRxiv2022

Theta band-power shapes amyloid-driven longitudinal EEG changes in pre-clinical Alzheimer's Disease

Alzheimers Disease (AD) includes progressive symptoms spread along a continuum of pre-clinical (pre-AD) and clinical stages. Pre-AD refers to cognitively healthy individuals with presence of positive pathophysiological biomarkers of AD (i.e., markers of amyloidopathy and tauopathy). Although numerous studies uncovered the neuro-cognitive changes of AD, very little is known on the natural history of brain lesions and modifications of brain networks of pre-AD. To address this issue, we analysed resting-state EEG data of 318 cognitively healthy individuals with subjective memory complains from the INSIGHT-preAD cohort at the time of their first visit (M0) and two-years later (M24). Using 18F-florbetapir PET-scanner, subjects were stratified between amyloid positive (A-; n=230) and amyloid negative (A+; n=88) groups. Differences between A+ and A- individuals were estimated at source level in each band of the EEG power spectrum. At M0, we found an increase of theta-band power in the mid-frontal cortex in A+ compared to A-. No significant association was found between mid-frontal theta power and the individuals cognitive performance. While the very same effect was not replicated at M24, theta-band power increased in A+ relative to A- individuals in the posterior cingulate cortex and the pre-cuneus. Furthermore, alpha band revealed a peculiar decremental trend in posterior brain regions in the A+ relative to the A- group only at M24. These results provide the first source-level longitudinal evidence on the impact of brain amyloidosis on the EEG dynamics of a large-scale, monocentric cohort of pre-AD. Theta-band power increase over the mid-frontal and mid-posterior cortices suggests an hypoactivation of the default-mode network in individuals at-risk of AD and a non-linear longitudinal progression of the AD-spectrum.

neuroscience↗

bioRxiv2018

Low frequency and rare coding variation contributes to multiple sclerosis risk

Multiple sclerosis is a common, complex neurological disease, where almost 20% of risk heritability can be attributed to common genetic variants, including >230 identified by genome-wide association studies (Patsopoulos et al., 2017). Multiple strands of evidence suggest that the majority of the remaining heritability is also due to the additive effects of individual variants, rather than epistatic interactions between these variants, or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that as much as 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common variant signals, which highlight a key role for regulatory T cell homeostasis and regulation, IFN{gamma} biology and NF{kappa}B signaling in MS pathogenesis. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS.

genetics↗

bioRxiv2017

"A mosquito bites and a butterfly flies": a specific response type of frontal patients in a similarity task

BackgroundPatients with neurodegenerative diseases affecting the frontal lobes have difficulties in categorization tasks, such as the similarity tasks. They give two types of unusual response to the question: \"In what way are an orange and a banana alike?\", either a differentiation (\"one is yellow, the other is orange\") or a concrete similarity (\"they are sweet\").\n\nObjectiveTo characterize the categorization deficit of frontal patients and develop a short diagnostic tool to assess the nature of these difficulties.\n\nMethodWe analyzed the responses provided by frontal and non-frontal neurodegenerative patients in a novel verbal similarity task (SimiCat). We included 40 frontal patients with behavioral variant fronto-temporal dementia (bvFTD) and progressive supranuclear palsy (PSP), 23 patients with Alzheimers disease (AD) and 41 healthy matched controls. Responses that did not correspond to the expected taxonomic category (e.g.: fruits) were considered as errors.\n\nResultsAll patients groups were impaired at the SimiCat test compared to controls. Differentiation errors were specific of frontal patients. Receiver operating characteristic analyses showed that a cut-off of two differentiation errors or more achieved 85% sensitivity of 100% specificity to discriminate bvFTD from AD. A short version of the test (<5 min) showed similar discriminative validity as the full version.\n\nConclusionDifferentiation responses were specific of frontal patients. The SimiCat demonstrates good discriminative validity to differentiate bvFTD and AD. The short version of the test is a promising diagnostic tool that will need validation in future studies.

neuroscience↗

bioRxiv2017

The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility

AbstractWe assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.\n\nOne Sentence SummaryWe report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.

genetics↗